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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1208-7631 | Registry Identifier | WHO | |
| JapicCTI-183885 | Registry Identifier | JapicCTI |
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The purposes of this study are to evaluate BE between a single-dose of TAK-438ASA tablet versus a single-dose combination of TAK-438 tablet 10 milligram (mg) and aspirin enteric-coated tablet 100 mg in Japanese healthy adult men (Study 1), and to evaluate the effects of food on the pharmacokinetics of TAK-438ASA tablet in Japanese healthy adult men (Study 2).
The drug under investigation in this study is called TAK-438ASA. TAK-438ASA is being tested in Japanese healthy adult men. This study consists of two studies to evaluate bioequivalence (Study 1) and the effects of food (Study 2). Study 1 (split into a Pilot phase and a Pivotal phase) will look at bioequivalence between a single-dose of TAK-438ASA tablet versus a single-dose combination of TAK-438 tablet 10 mg and aspirin enteric-coated tablet 100 mg. Study 2 will look at the effects of food on the pharmacokinetics of TAK-438ASA tablet.
The study will enroll up to 440 participants in total (Study 1 + 2). For Study 1, 12 participants per group (24 participants in total) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups for the pilot study to estimate the sample size of Pivotal study. After pilot study, 202 participants as a maximum per group (404 participants in total) will be randomly assigned to one of the two treatment groups:
For Study 2, 6 participants per group (12 participants in total) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pilot phase of Study 1,TAK-438ASA + TAK-438 and Aspirin | Experimental | One TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 1 in the Pilot phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 2 in the Pilot phase of Study 1 (Day 16). |
|
| Pilot phase of Study 1,TAK-438 and Aspirin + TAK-438ASA | Experimental | One TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 1 in the Pilot phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by, one TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 2 in the Pilot phase of Study 1 (Day 16). |
|
| Pivotal phase of Study 1, TAK-438ASA + TAK-438 and Aspirin | Experimental | One TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 1 in the Pivotal phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 2 in the Pivotal phase of Study 1 (Day 16). |
|
| Pivotal phase of Study 1, TAK-438 and Aspirin + TAK-438ASA | Experimental | One TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 1 in the Pivotal phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 2 in the Pivotal phase of Study 1 (Day 16). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-438ASA | Drug | TAK-438ASA tablet. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438F) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | |
| Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | |
| Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose | |
| Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose | |
| Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fukuoka Mirai Hospital | Fukuoka | Japan |
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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Healthy male participants were enrolled in this 2-period cross-over design study to receive 1 of the 2 treatment sequences: fixed dose combination (FDC) of TAK-438 and aspirin (TAK-438ASA) or a free combination of TAK-438 and aspirin in Study 1, and to receive 1 of the 2 sequences: FDC of TAK-438ASA under fasted or fed conditions in Study 2.
Participants took part in the study at 1 investigative site in Japan from 8 March 2018 to 12 October 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pilot Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin | TAK-438 10 milligram (mg) and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 2. |
| FG001 | Pilot Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA | TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. |
| FG002 | Pivotal Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 2. |
| FG003 | Pivotal Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA | TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. |
| FG004 | Study 2, Sequence C: TAK-438ASA (Fasted + Fed Condition) | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of Period 2. |
| FG005 | Study 2, Sequence D: TAK-438ASA (Fed + Fasted Condition) | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (1 Day) |
| |||||||||||||
| Washout Period (at Least 14 Days) |
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| Period 2 (1 Day) |
|
The safety analysis set was defined as all participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Pilot Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin | TAK-438 10 milligram (mg) and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 2. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438F) | The pharmacokinetic (PK) analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1. | Posted | Geometric Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
|
Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pilot Study 1: TAK-438ASA | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 9, 2018 | Oct 9, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 25, 2018 | Oct 9, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C552956 | 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine |
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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| Study 2,TAK-438ASA (Fasted + Fed condition) | Experimental | One TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 1 in Study 2 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438ASA tablet, orally 30 minutes after breakfast, on Day 1 of Period 2 in Study 2 (Day 16). |
|
| Study 2,TAK-438ASA (Fed + Fasted condition) | Experimental | One TAK-438ASA tablet, orally 30 minutes after breakfast, on Day 1 of Period 1 in Study 2 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 2 in Study 2 (Day 16). |
|
| TAK-438 | Drug | TAK-438 tablet. |
|
| Aspirin | Drug | Aspirin enteric-coated tablet. |
|
| Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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|
| BG001 | Pilot Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA | TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. |
| BG002 | Pivotal Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 2. |
| BG003 | Pivotal Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA | TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. |
| BG004 | Study 2, Sequence C: TAK-438ASA (Fasted + Fed Condition) | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of Period 2. |
| BG005 | Study 2, Sequence D: TAK-438ASA (Fed + Fasted Condition) | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
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| Consumption of caffeine | Count of Participants | Participants |
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| Consumption of alcohol | Count of Participants | Participants |
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| Smoking classification | Count of Participants | Participants |
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| Pilot Study 1: TAK-438 and Aspirin |
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2. |
| OG002 | Pivotal Study 1: TAK-438ASA | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2. |
| OG003 | Pivotal Study 1: TAK-438 and Aspirin | TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2. |
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| Primary | Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Primary | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
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| Primary | Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | ng/mL | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
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| Secondary | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | The PK analysis set included all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1. | Posted | Mean | Standard Deviation | 1 per hour | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
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| Secondary | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
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| Secondary | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
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| Secondary | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available. | Posted | Mean | Standard Deviation | 1 per hour | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
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| Secondary | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | ng/mL | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | The PK analysis set included all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Geometric Mean | Standard Deviation | ng/mL | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Median | Full Range | hour | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | hour | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | microgram (mcg) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | percentage of dose | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | liter per hour (l/h) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
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| Secondary | Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | mcg | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. | Posted | Mean | Standard Deviation | percentage of dose | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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| Secondary | Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Data for CLR of Salicyluric acid was not calculated since the plasma concentration of Salicyluric acid was not measured. | Posted | Mean | Standard Deviation | l/h | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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|
| 0 |
| 24 |
| 0 |
| 24 |
| 1 |
| 24 |
| EG001 | Pilot Study 1: TAK-438 and Aspirin | TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2. | 0 | 23 | 0 | 23 | 0 | 23 |
| EG002 | Pivotal Study 1: TAK-438ASA | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2. | 0 | 237 | 0 | 237 | 8 | 237 |
| EG003 | Pivotal Study 1: TAK-438 and Aspirin | TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2. | 0 | 239 | 0 | 239 | 3 | 239 |
| EG004 | Study 2: TAK-438ASA Fasted | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2. | 0 | 12 | 0 | 12 | 1 | 12 |
| EG005 | Study 2: TAK-438ASA Fed | TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of either Period 1 or 2. | 0 | 12 | 0 | 12 | 0 | 12 |
| Pharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Liver function test abnormal | Investigations | MedDRA (21.0) | Systematic Assessment |
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Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
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| Male |
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|
|
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|
|
| LSM Difference |
| 0.0912 |
| 2-Sided |
| 90 |
| 0.0399 |
| 0.1424 |
| Equivalence |
Pivotal Study 1: The difference in the LSM between study medications (TAK-438ASA tablet - concomitant administration of TAK-438 tablet and aspirin enteric-coated tablet) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model will include a log-transformed (natural log) analysis variable as the dependent variable, and study medication, sequence, and period as independent variables. |
|
| LSM Difference |
| 0.2293 |
| 2-Sided |
| 90 |
| 0.1519 |
| 0.3068 |
| Equivalence |
Pivotal Study 1: The difference in the LSM between study medications (TAK-438ASA tablet - concomitant administration of TAK-438 tablet and aspirin enteric-coated tablet) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and study medication, sequence, and period as independent variables. |
|
| LSM Difference |
| 0.0654 |
| 2-Sided |
| 90 |
| 0.0141 |
| 0.1167 |
| Equivalence |
Pivotal Study 1: The difference in the LSM between study medications (TAK-438ASA tablet - concomitant administration of TAK-438 tablet and aspirin enteric-coated tablet) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and study medication, sequence, and period as independent variables. |
|
| LSM Difference |
| -0.1674 |
| 2-Sided |
| 90 |
| -0.2084 |
| -0.1264 |
| Equivalence |
Pivotal Study 1: The difference in the LSM between study medications (TAK-438ASA tablet - concomitant administration of TAK-438 tablet and aspirin enteric-coated tablet) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and study medication, sequence, and period as independent variables. |
|
| LSM Difference |
| -0.1366 |
| 2-Sided |
| 90 |
| -0.1730 |
| -0.1002 |
| Equivalence |
Pivotal Study 1: The difference in the LSM between study medications (TAK-438ASA tablet - concomitant administration of TAK-438 tablet and aspirin enteric-coated tablet) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and study medication, sequence, and period as independent variables. |
|
| LSM Difference |
| -0.0020 |
| 2-Sided |
| 90 |
| -0.0463 |
| 0.0424 |
| Equivalence |
Pivotal Study 1: The difference in the LSM between study medications (TAK-438ASA tablet - concomitant administration of TAK-438 tablet and aspirin enteric-coated tablet) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and study medication, sequence, and period as independent variables. |
| M-I |
|
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| M-II |
|
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| M-III |
|
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| M-IV-Sul |
|
|
| M-II |
|
| M-III |
|
| M-IV-Sul |
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| M-II |
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| M-III |
|
| M-IV-Sul |
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| M-II |
|
| M-III |
|
| M-IV-Sul |
|
| M-II |
|
| M-III |
|
| M-IV-Sul |
|
| M-I |
|
|
| M-II |
|
|
| M-III |
|
|
| M-IV-Sul |
|
|
| LSM Difference | 0.0140 | 2-Sided | 90 | -0.0639 | 0.0918 | Equivalence | Salicylic acid: The difference in the LSM between dosing condition (TAK-438ASA tablet taken in a fed [30 minutes after starting breakfast] - TAK-438ASA tablet taken in a fasted [without breakfast] condition) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and dosing condition, sequence, and period as independent variables. |
| LSM Difference | 0.0137 | 2-Sided | 90 | -0.0712 | 0.0986 | Equivalence | Salicylic acid: The difference in the LSM between dosing condition (TAK-438ASA tablet taken in a fed [30 minutes after starting breakfast] - TAK-438ASA tablet taken in a fasted [without breakfast] condition) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and dosing condition, sequence, and period as independent variables. |
| LSM Difference | 0.0201 | 2-Sided | 90 | -0.0690 | 0.1092 | Equivalence | Salicylic acid: The difference in the LSM between dosing condition (TAK-438ASA tablet taken in a fed [30 minutes after starting breakfast] - TAK-438ASA tablet taken in a fasted [without breakfast] condition) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and dosing condition, sequence, and period as independent variables. |
| LSM Difference | 0.1969 | 2-Sided | 90 | 0.1065 | 0.2873 | Equivalence | Salicylic acid: The difference in the LSM between dosing condition (TAK-438ASA tablet taken in a fed [30 minutes after starting breakfast] - TAK-438ASA tablet taken in a fasted [without breakfast] condition) and the two-sided 90% CI were provided using a crossover ANOVA model. The ANOVA model included a log-transformed (natural log) analysis variable as the dependent variable, and dosing condition, sequence, and period as independent variables. |
| M-II |
|
| M-III |
|
| M-IV-Sul |
|
| M-II |
|
| M-III |
|
| M-IV-Sul |
|
| M-II |
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| M-III |
|
| M-IV-Sul |
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| Salicyluric acid |
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| Salicyluric acid |
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